Protein Turnover Flashcards
What is protein turnover?
Protein turnover is the balance between protein breakdown and protein synthesis in the animal body
What is nitrogen balance?
Nitrogen balance is the balance between protein (nitrogen) intake and protein (nitrogen) loss in the body
What is muscle protein turnover?
Continuous synthesis and breakdown of body proteins
Replacement of old or mis-folded proteins
Proteins are regularly assembled, positioned in the cell, and eventually replaced with a newly synthesized protein, in a process known as protein turnover (eg balance between protein synthesis and degradation)
Muscle proteins are constantly turning over (broken down and synthesized)
Newly protein synthesis process not only occurs in the case of muscle hypertrophy
A critical and continuous balance exists between protein synthesis and protein degration in muscle cells
Growth = protein synthesis > protein degradation
Why does the body degrade muscle proteins?
Controls key physiological functions where cellular components need to be degraded and recycled
Required to degrade mis-folded or de-folded proteins, which would otherwise be capable of forming insoluble aggregates
Protein degradation ensures unnecessary proteins are removed from the cellular environment when they are no longer needed or damaged or faulty in someway
When a cell is unable to degrade abnormal or unnecessary proteins, these proteins can accumulate within the cellular environment, leading to many diseases
Magnitude of protein turnover
The dial rates of protein synthesis represent 2-8% of total body protein
The equivalent of the protein mass of the animal is replaced every:
- 8days for young pigs
- 18 days for dairy cows
- 30 days for adult humans
Muscle protein turnover
Turnover is slow
Muscle proteins slowly degrade and replaced without loss of function
Myosin half life 54 days (time for 50% degradation)
Protein that degrade other proteins called proteolytic enzymes
Strictly regulated
Sources of protein in ruminants
Produce via fermentation
Microbial proteins - microbes only live 15 minutes
Ammonia (NH3)
The rumen bacteria and Protozoa (a lesser extent) can grow and reproduce just by using NH3 instead of protein as a suitable nitrogen source
NH3 gets absorbed by the animal and detoxified in the liver, converting it into urea. urea is either expelled in the urine or feces, or it is recycled back into the rumen
Autophagy
Cells also use autophagy to eliminate damaged proteins and cell organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging
Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly
Mutations in autophagy genes can cause genetic disease
Disturbances in the autophagic machinery have also been linked to cancer
Proteolytic enzymes
Lysosomal system
Ubiquitin-proteasome system (UPS)
Calpains
Matrix metalloproteinases
Lysosomes in cellular digestion
Lysosomes are membrane bound vesicles in the cytoplasm
Manufactured by the Golgi apparatus and pinched off as single membrane vesicles
Enzymes (40-50 types) in lysosomes are acidic and typically hydrolytic
Located around the nuclei near sarcolemma in muscle
Extracellular proteins and phagocytoses bacteria undergo endocytosis and are completely degraded within lysosomes
Lysosomal enzymes types
Protein digesting enzymes (Cathepsins)
Phosphate esters (acid phosphatases)
CHO digesting enzymes
Nucleases (DNAse, RNAse)
Lipid digesting enzymes (esterase, spingomyelinase)
Lysosomal enzymes
Lysosomal pathway is mainly involved in degrading surface membrane proteins and endocytosed extracellular proteins, rather than having a major role in the normal turnover of cytosolic protein under normal conditions
Active at acidic pH; Lysosomal membrane compromised at low pH
Not strongly linked to Myofibrillar degradation
Linked to connective tissue solubility
Can degrade most Myofibrillar proteins, including myosin heavy chain
Cause degration at the Z-line, M-bands and A-bands
High protein turnover muscles have lists of cathepsins
Slow truth oxidative (type 1) muscle fibers have higher levels of cathepsins than fast twitch glycolytic (type IIB) muscle fibers
Ubiquitin-proteasome system (UPS) of protein degradation
Ubiquitin is a small 76-amino acid containing protein and it is the most highly conserved protein
Ubiquitin molecules are very stable and will not be changed when exposed to acid stress or heat shock
The major pathway of selective protein degradation in eukaryotic cells used Ubiquitin as a marker that targets cytosolic and nuclear proteins for rainier proteolysis
In all tissues, the majority of intracellular proteins are degraded by the Ubiquitin-proteasome pathway
It requires Ubiquitin and ATP
Mainly abnormal proteins and short lived proteins are degraded by this pathway
UPS
Proteins are marked for degradation by the attachment of Ubiquitin (Ubiquitin activating enzymes) to the amino group of the side chai of a lysine residue
Additional Ubiquitins (Ubiquitin conjugating enzyme and Ubiquitin protein ligase) are them added to form a multi-Ubiquitin chain
Poly-Ubiquitinated proteins are recognized and degraded by a larg, multi-subunit protease complex
Ubiquitin is released in the process, so it can be reused in another cycle
Note: Both the attachment of Ubiquitin and there degradation of marked proteins require energy in the form of ATP
26S Proteasome
The 26S proteasome is a large complex consisting protein of at lest 66 Proteins
Barrel shaped
‘housekeeping’ function - basal protein turnover
Eliminated abnormal proteins
Main proteolytic pathway during muscle wasting due to nutritional restriction
